{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:35:49Z","timestamp":1792082149261,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271561"],"award-info":[{"award-number":["82271561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301708"],"award-info":[{"award-number":["82301708"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Current antidepressants face limitations due to the blood\u2013brain barrier (BBB), systemic side effects and delayed onset. Here, we engineered an intranasal thermosensitive hydrogel (EVs@IN) encapsulating\n                    <jats:italic>Chlorella vulgaris<\/jats:italic>\n                    \u2010derived extracellular vesicles (EVs) for sustained nose\u2010to\u2010brain delivery. EVs@IN significantly enhanced nasal mucosal retention and facilitated targeted transport of EVs to the hippocampus via olfactory pathways, while minimizing pulmonary exposure and clearance. In mouse models of depression (LPS\u2010induced and CUMS), intranasal EVs@IN elicited rapid and potent alleviation of depressive\u2010 and anxiety\u2010like behaviours. Mechanistically, EVs modulated astrocyte phenotypic transformation, reducing the release of neurotoxic complement C3 and suppressing neuroinflammation. Concurrently, they activated the Nrf2\u2010Pgc\u20101\u03b1 pathway, enhanced antioxidant defences (elevated SOD and GSH), mitigated oxidative stress and restored synaptic plasticity and neurogenesis in the hippocampus. Furthermore, we demonstrated the capacity of EVs to serve as efficient drug carriers for brain delivery. EVs@IN exhibited excellent long\u2010term biocompatibility in vivo. Our findings establish plant\u2010derived EVs within a sustained\u2010release intranasal platform as a promising, scalable and BBB\u2010bypassing strategy for the rapid treatment of depression and potentially other neuropsychiatric disorders.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70198","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T18:30:16Z","timestamp":1763490616000},"source":"Crossref","is-referenced-by-count":16,"title":["Nose\u2010to\u2010Brain Delivery of\n                    <i>Chlorella vulgaris<\/i>\n                    Extracellular Vesicles for Antidepressant Effects"],"prefix":"10.1002","volume":"14","author":[{"given":"Kangyu","family":"Jin","sequence":"first","affiliation":[{"name":"Eye Center, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"Institute of Translational Medicine Zhejiang University  Hangzhou 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 Hangzhou China"},{"name":"Zhejiang Key Laboratory of Precision Psychiatry  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiying","family":"Tong","sequence":"additional","affiliation":[{"name":"Zhejiang University\u2010University of Edinburgh Institute (ZJU\u2010UoE Institute), Zhejiang University School of Medicine Zhejiang University  Haining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangjian","family":"Qi","sequence":"additional","affiliation":[{"name":"Songjiang Research Institute Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, the First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"Zhejiang Key Laboratory of Precision Psychiatry  Hangzhou 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